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Increasing familiarity with advanced endoscopic excision techniques allows for more colorectal lesions to be removed without major surgery. Endoscopic excision with negative margins is adequate for most polyps and low-risk T1 cancers. The use of modern polyp classification techniques based on size, morphology and pit pattern by an experienced endoscopist allow for an optical diagnosis of these lesions and can predict, with high accuracy, which lesions contain malignant disease and the level of invasion. A surgeon endoscopist must be able to recognize which complex polyps can be resected with advanced polypectomy techniques and which require upfront surgery. We aimed to provide an overview of polyp classification techniques to help surgeons select the correct treatment algorithm for advanced colorectal lesions based on their visual characteristics at index endoscopy., Widespread screening has increased the detection of early-stage colorectal cancers. Data from the United Kingdom show that nearly 10% of all malignant colon lesions will be found inside polyps. (1) [...]

Although the laboratory information system has largely solved the problem of storing anatomic pathology reports and disseminating their contents across the healthcare system, the retrospective query of anatomic pathology reports remains an area for improvement across laboratory information system vendors. Our institution desired the ability to query our repository of anatomic pathology reports for clinical, operational, research, and educational purposes. To address this need, we developed a full-text anatomic pathology search tool using the business intelligence software, Tableau. Our search tool allows users to query the 333,685 anatomic pathology reports from our institutional clinical relational database using the business intelligence tool's built-in regular expression functionality. Users securely access the search tool using any web browser, thereby avoiding the cost of installing or maintaining software on users' computers. This tool is laboratory information system vendor agnostic and as many institutions already subscribe to business intelligence software, we believe this solution could be easily reproduced at other institutions and in other clinical departments.

The modern management of rectal cancers continues to evolve. With the release of data from new landmark randomized controlled trials (RAPIDO, PRODIGE-23), total neoadjuvant therapy (TNT) has moved to the forefront of locally advanced rectal cancer treatment and is considered a standard option in selected patients. Total neoadjuvant therapy promises enhanced systemic disease control, better treatment adherence and less time with an ostomy. However, TNT as currently described encompasses a number of different potential treatment options that differ significantly in terms of their radiation dosage, chemotherapy regimen and order of treatments administered. Being familiar with TNT regimens will be important for rectal cancer surgeons to appropriately advocate for their patients and optimize their outcomes. This article serves as a primer for the general surgeon and offers a pragmatic overview of the indications, realistic expected benefits and potential downsides of each TNT regimen., For 15 years, the standard of care for locally advanced (clinical T3-4 or N-positive) rectal cancer in North America has consisted of neoadjuvant therapy (radiation or chemoradiotherapy) followed by total [...]

Context.--There has long been debate about whether and when there may be a shortage of pathologists in the United States. One way to assess this is to survey the hiring experiences of pathology practices. A 2018 survey revealed a strong demand for pathologists, with expectations of continued strength. This study updates that prior analysis using data from a 2021 survey of pathology practice leaders. Objective.--To assess the US pathologist job market and examine implications. Design.--We analyzed data from the 2021 College of American Pathologists Practice Leader Survey. This survey queried practice leaders, including regarding the hiring of pathologists, the level of experience being sought, success in filling positions, and expectations for hiring in the next 3 years. Results.--Among the 375 surveyed practice leaders (about one-third of all US pathology practices), 282 provided information about pathologist hiring in 2021. A total of 157 of these 282 practices (55.7%) sought to hire at least 1 pathologist in 2021, up from 116 of 256 practices (45.3%) in 2017; the mean number of pathologists hired per practice also increased. In 2021, a total of 175 of 385 positions (45.5%) were to fill new positions, compared with 95 of 249 positions (38.2%) in 2017. Most practice leaders were comfortable hiring pathologists with less than 2 years of posttraining experience. Practice leaders anticipated continued strong demand for hiring pathologists during the next 3 years. Conclusions.--Our analysis confirms that the demand in pathologist hiring is strong and much increased from 2017. We believe, in combination with other job market indicators, that demand may outstrip the supply of pathologists, which is limited by the number of trainees and has remained constant during the past 20 years. doi: 10.5858/arpa.2022-0023-CP, About 20 years ago, a future shortage in pathologists was predicted as a consequence of the closure of residency programs. (1,2) A decade later, some of the authors of the [...]

The Drosophila ovary is a widely used model for germ cell and somatic tissue biology. Here we use single-cell RNA-sequencing (scRNA-seq) to build a comprehensive cell atlas of the adult Drosophila ovary that contains transcriptional profiles for every major cell type in the ovary, including the germline stem cells and their niche cells, follicle stem cells, and previously undescribed subpopulations of escort cells. In addition, we identify Gal4 lines with specific expression patterns and perform lineage tracing of subpopulations of escort cells and follicle cells. We discover that a distinct subpopulation of escort cells is able to convert to follicle stem cells in response to starvation or upon genetic manipulation, including knockdown of escargot, or overactivation of mTor or Toll signalling.

BackgroundThe global COVID-19 pandemic brings new challenges to otolaryngology resident education. Surgical volume and clinic visits are curtailed, personal protective equipment for operating room participation is restricted, and the risk of COVID-19 disease transmission during heretofore routine patient care is the new norm.MethodsWe describe a small-team "cohorting" protocol including guidelines for faculty and resident in common clinical scenarios with attention paid to the risk of common otolaryngologic procedures.ResultsA rotating small-team approach was implemented at each clinical site, limiting interaction between department members but providing comprehensive coverage. Faculty were involved at the earliest phase of clinical interactions. Guidelines delineated faculty and resident roles based on risk stratification by patient COVID status and anticipated procedures. Special consideration was given to high-risk procedures such as endoscopy and tracheotomy.ConclusionsA small-team-based approach with guidelines for faculty/resident roles may mitigate risk while optimizing patient care and maximizing education.

[This corrects the article DOI: 10.1371/journal.pone.0226197.].

Intrinsically photosensitive melanopsin retinal ganglion cells (mRGCs) are crucial for non-image forming functions of the eye, including the photoentrainment of circadian rhythms and the regulation of the pupillary light reflex (PLR). Chromatic pupillometry, using light stimuli at different wavelengths, makes possible the isolation of the contribution of rods, cones, and mRGCs to the PLR. In particular, post-illumination pupil response (PIPR) is the most reliable pupil metric of mRGC function. We have previously described, in post-mortem investigations of AD retinas, a loss of mRGCs, and in the remaining mRGCs, we demonstrated extensive morphological abnormalities. We noted dendrite varicosities, patchy distribution of melanopsin, and reduced dendrite arborization. In this study, we evaluated, with chromatic pupillometry, the PLR in a cohort of mild-moderate AD patients compared to controls. AD and controls also underwent an extensive ophthalmological evaluation. In our AD cohort, PIPR did not significantly differ from controls, even though we observed a higher variability in the AD group and 5/26 showed PIPR values outside the 2 SD from the control mean values. Moreover, we found a significant difference between AD and controls in terms of rod-mediated transient PLR amplitude. These results suggest that in the early stage of AD there are PLR abnormalities that may reflect a pathology affecting mRGC dendrites before involving the mRGC cell body. Further studies, including AD cases with more severe and longer disease duration, are needed to further explore this hypothesis.

BACKGROUND: Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the bodys circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimers disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic pupillometry may be a potential biomarker for early diagnosis and progression of AD. METHODS: We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm. RESULTS: Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls. CONCLUSIONS: The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.

Objective: The objective of this study was to develop and assess multidisciplinary advanced surgical planning (ASP) sessions using three dimensional (3D) printed models for cervicothoracic slide tracheoplasty (CST). We hypothesized that these sessions would improve surgeon confidence, streamline intraoperative planning, and highlight the utility of 3D modeling. Methods: 3D‐printed patient‐specific trachea models were used in pre‐operative ASP sessions consisting of a multidisciplinary case discussion and hands‐on slide tracheoplasty simulation. Participants completed a survey rating realism, utility, impact on the final surgical plan, and pre‐ and post‐session confidence. Statistical analysis was performed via Wilcoxon and Kruskal‐Wallis tests. Results: Forty‐eight surveys were collected across nine sessions and 27 different physicians. On a 5‐point Likert scale, models were rated as "very realistic", "very useful" (both median of 4, IQR 3–4 and 4–5, respectively). Overall confidence increased by 1.4 points (+/− 0.7, p < 0.0001), with the largest change seen in those with minimal prior slide tracheoplasty experience (p = 0.005). Participants felt that the sessions "strongly" impacted their surgical plan or anticipated performance (median 4, IQR 4–5), regardless of training level or experience. Conclusion: 3D‐printed patient‐specific models were successfully implemented in ASP sessions for CST. Models were deemed very realistic and very useful by surgeons across multiple specialties and training levels. Surgical planning sessions also strongly impacted the final surgical plan and increased surgeon confidence for CST. Level of Evidence: 4 Laryngoscope, 134:3395–3401, 2024 [ABSTRACT FROM AUTHOR]

Over the millennia, patterns of food consumption have changed; however, foods were always whole foods. Ultra-processed foods (UPFs) have been a very recent development and have become the primary food source for many people. The purpose of this review is to propose the hypothesis that, forsaking the evolutionary dietary environment, and its complex milieu of compounds resulting in an extensive metabolome, contributes to chronic disease in modern humans. This evolutionary metabolome may have contributed to the success of early hominins. This hypothesis is based on the following assumptions: (1) whole foods promote health, (2) essential nutrients cannot explain all the benefits of whole foods, (3) UPFs are much lower in phytonutrients and other compounds compared to whole foods, and (4) evolutionary diets contributed to a more diverse metabolome. Evidence will be presented to support this hypothesis. Nutrition is a matter of systems biology, and investigating the evolutionary metabolome, as compared to the metabolome of modern humans, will help elucidate the hidden connections between diet and health. The effect of the diet on the metabolome may also help shape future dietary guidelines, and help define healthy foods. [ABSTRACT FROM AUTHOR]

Serrated polyps (SPs) were once considered benign, clinically unimportant lesions. However, it is now recognized that through the serrated neoplasia pathway (SNP), SPs play a role in the development of 15%-30% of cases of colorectal cancers (CRC). Furthermore, a high proportion of postcolonoscopy CRCs are believed to arise from SNP. Serrated polyps are classified into hyperplastic polyps, sessile serrated lesions, sessile serrated lesions with dysplasia, traditionally serrated adenomas, and unclassified serrated adenoma, each with a distinct morphological and molecular profile. Despite improved understanding, SPs remain a clinical challenge owing to evolving terminology, frequent pathologic misclassification, endoscopic underdetection, and high rates of incomplete removal. Surgeon endoscopists and surgeons who perform colorectal procedures will undoubtedly come across patients with SPs, and this paper summarizes some of the clinical challenges they will encounter. We also discuss the diagnosis and management of patients with serrated polyposis syndrome (SPS)., Historically, all serrated polyps (SPs) were thought to have no malignant potential. However, It is now recognized that up to 30% of sporadic colorectal cancers (CRCs) may arise from SPs [...]

Context.--Smart glasses are a wearable technology that enable hands-free data acquisition and entry. Objective.--To develop a surgical pathology grossing application on a smart glass platform. Design.--An existing logistics software for the Google Glass Enterprise smart glass platform was used to create surgical pathology grossing protocols. The 2 grossing protocols were developed to simulate grossing a complex (heart) and a simple (kidney) specimen. For both protocols, users were visually prompted by the smart glass device to perform each task, record measurements, or document the field of view. In addition to measuring the total time of the protocol performance, each substep within the protocol was automatically recorded. Subsequently, a report was generated that contained the dictation, images, voice recordings, and the timing of each step. The application was tested by 3 users using the 2 grossing protocols. The users were tracked across 3 grossing procedures for each protocol. Results.--For the complex specimen grossing the average time across repeated procedures was not significantly different between users (P > .99). However, when grossing times of the complex specimen were compared for repeated performances of the same user, a significant reduction in grossing times was observed with each repetition (P = .002). For the simple specimen, the average grossing time across multiple attempts was different among users (P = .03); however, no improvement in grossing time was observed with repeated performance (P = .499). Conclusions.--Augmented reality based grossing applications can provide automated data collection to track the changes in grossing performance over time. doi: 10.5858/arpa.2020-0090-OA, In the last decade there has been a rapid advancement in the use of information and communication technologies to empower the practice of medicine. Wearable smart glasses, such as Google [...]

The systematic sequencing of the cancer genome has led to the identification of numerous genetic alterations in cancer. However, a deeper understanding of the functional consequences of these alterations is necessary to guide appropriate therapeutic strategies. Here, we describe Onco-GPS (OncoGenic Positioning System), a data-driven analysis framework to organize individual tumor samples with shared oncogenic alterations onto a reference map defined by their underlying cellular states. We applied the methodology to the RAS pathway and identified nine distinct components that reflect transcriptional activities downstream of RAS and defined several functional states associated with patterns of transcriptional component activation that associates with genomic hallmarks and response to genetic and pharmacological perturbations. These results show that the Onco-GPS is an effective approach to explore the complex landscape of oncogenic cellular states across cancers, and an analytic framework to summarize knowledge, establish relationships, and generate more effective disease models for research or as part of individualized precision medicine paradigms.